The majority of cancer deaths is due to the dissemination of tumor cells and subsequent formation of metastatic lesions. The detection of circulating tumor cells is therefore expected to be a powerful tool in the evaluation of cancer prognosis. Current strategies for detecting and isolating disseminated tumor cells are technically limited and still suffer from very low sensitivity and specificity, which is in part due to high serum concentrations of tumor-associated antigens (TAAs). Here, we developed a cellular biosensor that selectively targets membranebound carcinoembryonic antigen (CEA) of colorectal cancer in the presence of the soluble CEA. The signaling device of the sensor is a recombinant immunoreceptor, which is modularily composed of an extracellular single chain antibody fragment (scFv) for binding and an intracellular CD3zeta signaling domain. The receptor is expressed in genetically modified Jurkat T-cells, equipped with an intracellular NFAT-luciferase indicator, which enables the biosensor to generate a light signal after antigen-specific crosslinking of the immunoreceptor on the cell surface. The biosensor with specificity for CEA was activated upon binding of CEA coated on sepharose beads while ignoring high levels of soluble antigen. This demonstrates the feasibility of the biosensor for specific detection of membrane-bound CEA in the presence of high serum concentrations of CEA as found in cancer patients during progression of the disease. By using the fluorescent Ca2+-sensitive Cameleon protein as reporter, the biosensor acts in nearly real time. While these biosensors detect corpuscular CEA, soluble CEA is detected by a combined costimulatory CD28-CD3zeta signalling domain. Taken together the biosensor provides a versatile system to detect circulating tumor cells in a fast, highly specific and sensitive fashion by clearly discriminating corpuscular versus soluble antigen. We moreover adopted the biosensor concept to an immunotherapeutic approach to induce the production of the immune stimulatory cytokine IL-12 in human T-lymphocytes upon specific binding to CEA+ tumor cells. NFAT-triggered IL-12 and the CEA-specific immunoreceptor were coexpressed in T-cells which secrete IL-12 upon receptor binding to CEA. Moreover, the secretion of IFN-gamma and cytolysis of CEA+ tumor cells is increased compared to T cells with anti-CEA receptors only. Recombinant immunoreceptor triggered secretion of a heterologous protein thereby provides a stategy for the concentration of an immunotherapeutic adjuvans specifically at the tumor site, while preventing systemic toxicity.